Early Goal-directed Therapy During Endovascular Coiling Procedures Following Aneurysmal Subarachnoid Hemorrhage: A Pilot Prospective Randomized Controlled Study.

BACKGROUND: Maintenance of euvolemia and cerebral perfusion are recommended for the prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). We conducted a pilot randomized controlled study to assess the feasibility and efficacy of goal-directed therapy (GDT) to correct fluid and hemodynamic derangements during endovascular coiling in patients with aSAH. METHODS: This study was conducted between November 2015 and February 2019 at a single tertiary center in Canada. Adult patients with aSAH within 5 days of aneurysm rupture were randomly assigned to receive either GDT or standard therapy during endovascular coiling. The incidence of dehydration at presentation and the efficacy of GDT were evaluated. RESULTS: Forty patients were allocated to receive GDT (n=21) or standard therapy (n=19). Sixty percent of all patients were found to have dehydration before the coiling procedure commenced. Compared with standard therapy, GDT reduced the duration of intraoperative hypovolemia (mean difference 37.6 [95% confidence interval, 6.2-37.4] min, P=0.006) and low cardiac index (mean difference 30.7 [95% confidence interval, 9.5-56.9] min, P=0.035). There were no differences between the 2 treatment groups with respect to the incidence of vasospasm, stroke, death, and other complications up to postoperative day 90. CONCLUSIONS: A high proportion of aSAH patients presented at the coiling procedure with dehydration and a low cardiac output state; these derangements were more likely to be corrected if the GDT algorithm was used. Compared with standard therapy, use of the GDT algorithm resulted in earlier recognition and more consistent treatment of dehydration and hemodynamic derangement during endovascular coiling.

Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients. METHODS: Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS: Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI [-0.5 to 0.07] I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI [0.20 to 0.64] I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI [1.17 to 3.37], I2 = 49); fatigue (RR = 1.85, 95% CI [1.12 to 3.05], I2 = 0); difficulties with mentation (RR = 3.34, 95% CI [1.54 to 7.25], I2 = 0); and visual disturbances (RR = 5.72, 95% CI [1.94 to 16.91], I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements. CONCLUSIONS AND RELEVANCE: Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue. TRIAL REGISTRATION: PROSPERO CRD42016034040.

Gabapentinoids for chronic low back pain: a protocol for systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Chronic low back pain (CLBP) is a common condition and causes significant pain, distress and disability across the world. It is multifactorial in aetiology and is challenging to manage. Although the underlying mechanism of pain is predominantly non-specific, many argue that there is a substantial neuropathic pain element. Neuropathic pain is more severe, with significant disability. Gabapentinoids, including gabapentin and pregabalin, have proven efficacy in some neuropathic pain conditions. Despite no clear evidence, a substantial population of patients with CLBP are treated with gabapentinoids. OBJECTIVES: We aim to assess whether the use of gabapentinoids is effective and safe in the treatment of predominant CLBP, by conducting a systematic review and meta-analysis of randomised control trials (RCTs). METHODOLOGY: We will search the databases of MEDLINE, EMBASE and Cochrane for RCTs published in English language and have used gabapentinoids for the treatment of CLBP. Study selection and data extraction will be performed independently by paired reviewers using structured electronic forms, piloted between pairs of reviewers. The review outcomes will be guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief as the primary outcome. We propose to carry out meta-analysis if there are three or more studies in a particular outcome domain, using a random effects model. Pooled outcomes will be reported as weighted mean differences or standardised mean differences and risk ratios with their corresponding 95% CIs, for continuous outcomes and dichotomous outcomes, respectively. Rating of quality of evidence will be reported using GRADE summary of findings table. DISCUSSION: The proposed systematic review will be able to provide valuable evidence to help decision-making in the use of gabapentinoids for the treatment of CLBP. This will help advance patient care and potentially highlight limitations in existing evidence to direct future research. ETHICS AND DISSEMINATION: Being a systematic review, this study would not necessitate ethical review and approval. We plan to report and publish our study findings in a high impact medical journal, with online access. TRIAL REGISTRATION NUMBER: CRD42016034040.